CELL CYCLE AND APOPTOSIS GENES IN IMMUNOLOGIC SENESCENCE

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DESCRIPTION (Adapted from the Investigator's abstract): This application is based on the hypothesis that immunologic senescence of T-cells is the results of two concurrent and interrelated events. The T-cell repertoire is reshaped by an expanded memory lymphocyte pool. The memory T-cells themselves reach a refractory (anergic) state manifested by further resistance to further activation, cell cycle entry and apoptosis. The first effect is attributed to the dilution of naive cells by the accumulated memory phenotype cells that leads to overall repertoire constrictions. The second effect is attributed to a generational clock that records an allocated number of activations and cell divisions by memory T-cells before promoting replicative senescence primarily by the buildup of cyclin kinase inhibitors. These studies of cell cycle and apoptosis of aged T-cells will be instrumental to defining the molecular defects associated with immunologic senescence.